Gene therapy for liver enzyme deficiencies: What have we learned from models for Crigler–Najjar and tyrosinemia?

Expert Review of Gastroenterology and Hepatology

Volumn 1, Issue 1, 2007, Pages 155-171

  Nguyen, Tuan Huy ^a   Ferry, Nicolas ^a  

^a HÔTEL DIEU   (France)

Author keywords

AAV; adenovirus; Crigler Najjar; gene therapy; lentivirus; liver; liver repopulation; tyrosinemia; vector

Indexed keywords

GLUCURONOSYLTRANSFERASE; TYROSINE AMINOTRANSFERASE;

ANIMAL; CRIGLER NAJJAR SYNDROME; DISEASE MODEL; GENE THERAPY; HUMAN; REVIEW; TYROSINEMIA;

ANIMALS; CRIGLER-NAJJAR SYNDROME; DISEASE MODELS, ANIMAL; GENE THERAPY; GLUCURONOSYLTRANSFERASE; HUMANS; TYROSINE TRANSAMINASE; TYROSINEMIAS;

EID: 61549133962     PISSN: 17474124     EISSN: 17474132     Source Type: Journal    
DOI: 10.1586/17474124.1.1.155     Document Type: Article

References (128)

1. Mai G, Nguyen TH, Morel P et al. Treatment of fulminant liver failure by transplantation of microencapsulated primary or immortalized xenogeneic hepatocytes. Xenotransplantation 12 (6), 457–464 (2005).
2. Toso C, Ris F, Mentha G, Oberholzer J, Morel P, Majno P. Potential impact of in situ liver splitting on the number of available grafts. Transplantation 74 (2), 222–226 (2002).
3. Arbuthnot PB, Bralet MP, LeJossic C et al. In vitro and in vivo hepatoma cell-specific expression of a gene transferred with an adenoviral vector. Hum. Gene Ther. 7 (13), 1503–1514 (1996).
4. Bilbao R, Bustos M, Alzuguren P et al. A blood–tumor barrier limits gene transfer to experimental liver cancer: the effect of vasoactive compounds. Gene Ther. 7 (21), 1824–1832 (2000).
5. Gerolami R, Cardoso J, Bralet MP et al. Enhanced in vivo adenovirus-mediated gene transfer to rat hepatocarcinomas by selective administration into the hepatic artery. Gene Ther. 5 (7), 896–904 (1998).
6. Fox IJ, Roy-Chowdhury J. Hepatocyte transplantation. J. Hepatol. 40 (6), 878–886 (2004).
7. Grossman M, Rader DJ, Muller DWM et al. A pilot study of ex vivo gene therapy for homozygous familial hypercholesterolemia. Nat. Med. 11148–1154 (1995).
8. Michalopoulos G, DeFrances M. Liver regeneration. Science 276 (5309), 60–66 (1997).
9. Mignon A, Guidotti JE, Mitchell C et al. Selective repopulation of normal mouse liver by Fas/CD95-resistant hepatocytes. Nat. Med. 4 (10), 1185–1188 (1998).
10. Overturf K, Al-Dhalimy M, Tanguay R et al. hepatocytes corrected by gene therapy are selected in vivo in a murine model of hereditary tyrosinaemia type I. Nat. Genet. 12 (3), 266–273 (1996).
11. De Vree JM, Ottenhoff R, Bosma PJ, Smith AJ, Aten J, Oude Elferink RP. Correction of liver disease by hepatocyte transplantation in a mouse model of progressive familial intrahepatic cholestasis. Gastroenterology 119 (6), 1720–1730 (2000).
12. Yoshida Y, Tokusashi Y, Lee GH, Ogawa K. Intrahepatic transplantation of normal hepatocytes prevents Wilson’s disease in Long-Evans cinnamon rats. Gastroenterology 111 (6), 1654–1660 (1996).
13. Labrune P. Severe neonatal jaundice. Definition and management. Arch. Pediatr. 5 (10), 1162–1167 (1998).
14. Fox IJ, Chowdhury JR, Kaufman SS et al. Treatment of the Crigler–Najjar syndrome type I with hepatocyte transplantation. N. Engl. J. Med. 338 (20), 1422–1426 (1998).
15. Arias IM, Gartner LM, Cohen M, Ezzer JB, Levi AJ. Chronic nonhemolytic unconjugated hyperbilirubinemia with glucuronyl transferase deficiency. Clinical, biochemical, pharmacologic and genetic evidence for heterogeneity. Am. J. Med. 47 (3), 395–409 (1969).
16. Jansen PL. Diagnosis and management of Crigler–Najjar syndrome. Eur. J. Pediatr. 158, S89 –S94 (1999).
17. Gunn CH. Hereditary acholuric jaundice in a new mutant strain of rats. J. Hered. 29, 137–139 (1938).
18. Wu GY, Wu CH. Receptor-mediated gene delivery and expression in vivo. J. Biol. Chem 263, 14621–14624 (1988).
19. Chowdhury NR, Hays RM, Bommineni VR et al. Microtubular disruption prolongs the expression of human bilirubin-uridinediphosphoglucuronate-glucuronosyltransferase-1 gene transferred into Gunn rat livers. J. Biol. Chem 271 (4), 2341–2346 (1996).
20. Herweijer H, Wolff JA. Progress and prospects: naked DNA gene transfer and therapy. Gene Ther. 10 (6), 453–458 (2003).
21. Jia Z, Danko I. Single hepatic venous injection of liver-specific naked plasmid vector expressing human UGT1A1 leads to long-term correction of hyperbilirubinemia and prevention of chronic bilirubin toxicity in Gunn rats. Hum. Gene Ther. 16 (8), 985–995 (2005).
22. Danko I, Jia Z, Zhang G. Nonviral gene transfer into liver and muscle for treatment of hyperbilirubinemia in the Gunn rat. Hum. Gene Ther. 15 (12), 1279–1286 (2004).
23. Jia Z, Danko I. Long-term correction of hyperbilirubinemia in the Gunn rat by repeated intravenous delivery of naked plasmid DNA into muscle. Mol. Ther. 12 (5), 860–866 (2005).
24. Sawyer GJ, Dong X, Whitehorne M et al. Cardiovascular function following acute volume overload for hydrodynamic gene delivery to the liver. Gene Ther. (2007) (Epub ahead of print).
25. Alino SF, Herrero MJ, Noguera I, Dasi F, Sanchez M. Pig liver gene therapy by noninvasive interventionist catheterism. Gene Ther. 14, 334–343 (2007).
26. Kren BT, Parashar B, Bandyopadhyay P, Chowdhury NR, Chowdhury JR, Steer CJ. Correction of the UDP-glucuronosyltransferase gene defect in the Gunn rat model of Crigler–Najjar syndrome type I with a chimeric oligonucleotide. Proc. Natl Acad. Sci. USA 96 (18), 10349–10354 (1999).
27. Taubes G. Gene therapy. The strange case of chimeraplasty. Science 298 (5601), 2116–2120 (2002).
28. Sauter BV, Parashar B, Chowdhury NR et al. A replication-deficient rSV40 mediates liver-directed gene transfer and a long-term amelioration of jaundice in Gunn rats. Gastroenterology 119 (5), 1348–1357 (2000).
29. Jaffe HA, Danel C, Longenecker G et al. Adenovirus-mediated in vivo gene transfer and expression in normal rat liver. Nat. Genet. 1372–378 (1992).
30. Li QT, Kay MA, Finegold M, Stratford-Perricaudet LD, Woo SLC. Assessment of recombinant adenoviral vectors for hepatic gene therapy. Hum. Gene Ther. 4 (4), 403–409 (1993).
31. Askari FK, Hitomi Y, Mao M, Wilson JM. Complete correction of hyperbilirubinemia in the Gunn rat model of Crigler–Najjar syndrome type I following transient in vivo adenovirus-mediated expression of human bilirubin UDP-glucuronosyltransferase. Gene Ther. 3 (5), 381–388 (1996).
32. Li Q, Murphree SS, Willer SS, Bolli R, French BA. Gene therapy with bilirubin-UDP-glucuronosyltransferase in the Gunn rat model of Crigler–Najjar syndrome type I. Hum. Gene Ther. 9 (4), 497–505 (1998).
33. Ilan Y, Prakash R, Davidson A et al. Oral tolerization to adenoviral antigens permits long-term gene expression using recombinant adenoviral vectors. J. Clin. Invest. 99 (5), 1098–1106 (1997).
34. Ilan Y, Attavar P, Takahashi M et al. Induction of central tolerance by intrathymic inoculation of adenoviral antigens into the host thymus permits long-term gene therapy in Gunn rats. J. Clin. Invest. 98 (11), 2640–2647 (1996).
35. Takahashi M, Ilan Y, Chowdhury NR, Guida J, Horwitz M, Chowdhury JR. Long term correction of bilirubin-UDP-glucuronosyltransferase deficiency in Gunn rats by administration of a recombinant adenovirus during the neonatal period. J. Biol. Chem 271 (43), 26536–26542 (1996).
36. Ilan Y, Droguett G, Chowdhury NR et al. Insertion of the adenoviral E3 region into a recombinant viral vector prevents antiviral humoral and cellular immune responses and permits long-term gene expression. Proc. Natl Acad. Sci. USA 94 (6), 2587–2592 (1997).
37. Thummala NR, Ghosh SS, Lee SW et al. A non-immunogenic adenoviral vector, coexpressing CTLA4Ig and bilirubin-uridine-diphosphoglucuronateglucuronosyltransferase permits long-term, repeatable transgene expression in the Gunn rat model of Crigler–Najjar syndrome. Gene Ther. 9 (15), 981–990 (2002).
38. Schiedner G, Morral N, Parks RJ et al. Genomic DNA transfer with a high-capacity adenovirus vector results in improved in vivo gene expression and decreased toxicity. Nat. Genet. 18 (2), 180–183 (1998).
39. Brown BD, Shi CX, Powell S et al. Helper-dependent adenoviral vectors mediate therapeutic factor VIII expression for several months with minimal accompanying toxicity in a canine model of severe hemophilia A. Blood 103 (3), 804–810 (2004).
40. Ehrhardt A, Xu H, Dillow AM, Bellinger DA, Nichols TC, Kay MA. A gene-deleted adenoviral vector results in phenotypic correction of canine hemophilia B without liver toxicity or thrombocytopenia. Blood 102 (7), 2403–2411 (2003).
41. Toietta G, Mane VP, Norona WS et al. Lifelong elimination of hyperbilirubinemia in the Gunn rat with a single injection of helper-dependent adenoviral vector. Proc. Natl Acad. Sci. USA 102 (11), 3930–3935 (2005).
42. Brunetti-Pierri N, Palmer DJ, Beaudet AL, Carey KD, Finegold M, Ng P. Acute toxicity after high-dose systemic injection of helper-dependent adenoviral vectors into nonhuman primates. Hum. Gene Ther. 15, 35–46 (2004).
43. Raper SE, Chirmule N, Lee FS et al. Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. Mol. Genet. Metab. 80 (1–2), 148–158 (2003).
44. Brunetti-Pierri N, Stapleton GE, Palmer DJ et al. Pseudo-hydrodynamic delivery of helper-dependent adenoviral vectors into non-human primates for liver-directed gene therapy. Mol. Ther. 15 (4), 732–740 (2007).
45. Snyder RO, Miao C, Meuse L et al. Correction of hemophilia B in canine and murine models using recombinant adeno-associated viral vectors. Nat. Med. 5 (1), 64–70 (1999).
46. Manno CS, Arruda VR, Pierce GF et al. Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nat. Med. 12 (3), 342–347 (2006).
47. Vandenberghe LH, Wang L, Somanathan S et al. Heparin binding directs activation of T cells against adeno-associated virus serotype II capsid. Nat. Med. 12, 967–971 (2006).
48. Gao GP, Alvira MR, Wang L, Calcedo R, Johnston J, Wilson JM. Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy. Proc. Natl Acad. Sci. USA 99 (18), 11854–11859 (2002).
49. Gao GP, Lu Y, Sun X et al. High-level transgene expression in nonhuman primate liver with novel adeno-associated virus serotypes containing self-complementary genomes. J. Virol. 80 (12), 6192–6194 (2006).
50. Nathwani AC, Gray JT, McIntosh J et al. Safe and efficient transduction of the liver after peripheral vein infusion of self-complementary AAV vector results in stable therapeutic expression of human FIX in nonhuman primates. Blood 109 (4), 1414–1421 (2007).
51. Seppen J, Bakker C, de Jong B et al. Adeno-associated virus vector serotypes mediate sustained correction of bilirubin udp glucuronosyltransferase deficiency in rats. Mol. Ther. 13 (6), 1085–1092 (2006).
52. McCarty DM, Fu H, Monahan PE, Toulson CE, Naik P, Samulski RJ. Adeno-associated virus terminal repeat (TR) mutant generates self-complementary vectors to overcome the rate-limiting step to transduction in vivo. Gene Ther. 10 (26), 2112–2118 (2003).
53. McCarty DM, Monahan PE, Samulski RJ. Self-complementary recombinant adeno-associated virus (scAAV) vectors promote efficient transduction independently of DNA synthesis. Gene Ther. 8 (16), 1248–1254 (2001).
54. Mulligan R. The basic science of gene therapy. Science 260 (5110), 926–932 (1993).
55. Ferry N, Duplessis O, Houssin D, Danos O, Heard JM. Retroviral-mediated gene transfer into hepatocytes in vivo. Proc. Natl Acad. Sci. USA 88 (19), 8377–8381 (1991).
56. Tada K, Chowdhury NR, Neufeld D et al. Long-term reduction of serum bilirubin levels in Gunn rats by retroviral gene transfer in vivo. Liver Transpl. Surg. 4 (1), 78–88 (1998).
57. Kitten O, Cosset FL, Ferry N. Highly efficient retrovirus-mediated gene transfer into rat hepatocytes in vivo. Hum. Gene Ther. 81491–1494 (1997).
58. Izembart A, Aguado E, Gauthier O, Aubert D, Moullier P, Ferry N. In vivo retrovirus-mediated gene transfer to the liver of dogs results in transient expression and induction of a cytotoxic immune response. Hum. Gene Ther. 10 (18), 2917–2925 (1999).
59. Aubert D, Menoret S, Chiari E et al. Cytotoxic immune response blunts long-term transgene expression after efficient retroviral-mediated hepatic gene transfer in rat. Mol. Ther. 5 (4), 388–396 (2002).
60. Bellodi-Privato M, Aubert D, Pichard V, Myara A, Trivin F, Ferry N. Successful gene therapy of the Gunn rat by in vivo neonatal hepatic gene transfer using murine oncoretroviral vectors. Hepatology 42 (2), 431–438 (2005).
61. Naldini L, Blomer U, Gallay P et al. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272 (5259), 263–267 (1996).
62. Follenzi A, Ailles L, Bakovic S, Geuna M, Naldini L. Gene transfer by lentiviral vectors is limited by nuclear translocation and rescued by HIV-1 pol sequences. Nat. Genet. 25 (2), 217–222 (2000).
63. Tsui LV, Kelly M, Zayek N et al. Production of human clotting Factor IX without toxicity in mice after vascular delivery of a lentiviral vector. Nat. Biotechnol. 20 (1), 53–57 (2002).
64. Follenzi A, Battaglia M, Lombardo A, Annoni A, Roncarolo MG, Naldini L. Targeting lentiviral vector expression to hepatocytes limits transgene-specific immune response and establishes long-term expression of human antihemophilic Factor IX in mice. Blood 3030 (2003).
65. Pfeifer A, Kessler T, Yang M et al. Transduction of liver cells by lentiviral vectors: analysis in living animals by fluorescence imaging. Mol. Ther. 3 (3), 319–322 (2001).
66. Follenzi A, Sabatino G, Lombardo A, Boccaccio C, Naldini L. Efficient gene delivery and targeted expression to hepatocytes in vivo by improved lentiviral vectors. Hum. Gene Ther. 13 (2), 243–260 (2002).
67. Ohashi K, Park F, Kay MA. Role of hepatocyte direct hyperplasia in lentivirus-mediated liver transduction in vivo. Hum. Gene Ther. 13 (5), 653–663 (2002).
68. Park F, Ohashi K, Chiu W, Naldini L, Kay M. Efficient lentiviral transduction of liver requires cell cycling in vivo. Nat. Genet. 24 (1), 49–52 (2000).
69. Carbonaro DA, Jin X, Petersen D et al. In vivo transduction by intravenous injection of a lentiviral vector expressing human ADA into neonatal ADA gene knockout mice: a novel form of enzyme replacement therapy for ADA deficiency. Mol. Ther. 13 (6), 1110–1120 (2006).
70. VandenDriessche T, Thorrez L, Naldini L et al. Lentiviral vectors containing the human immunodeficiency virus type-1 central polypurine tract can efficiently transduce nondividing hepatocytes and antigen-presenting cells in vivo. Blood 100 (3), 813–822 (2002).
71. Seppen J, van der Rijt R, Looije N, van Til NP, Lamers WH, Oude Elferink RP. Long-term correction of bilirubin UDPglucuronyltransferase deficiency in rats by in utero lentiviral gene transfer. Mol. Ther. 8 (4), 593–599 (2003).
72. Nguyen TH, Aubert D, Bellodi-Privato M et al. Critical assessment of lifelong phenotype correction in hyperbilirubinemic Gunn rats after retroviral mediated gene transfer. Gene Ther. (2007) (Epub ahead of print).
73. Brown BD, Sitia G, Annoni A et al. In vivo administration of lentiviral vectors triggers a type I interferon response that restricts hepatocyte gene transfer and promotes vector clearance. Blood 109 (7), 2797–2805 (2006).
74. Cara A, Cereseto A, Lori F, Reitz MS Jr. HIV-1 protein expression from synthetic circles of DNA mimicking the extrachromosomal forms of viral DNA. J. Biol. Chem 271 (10), 5393–5397 (1996).
75. Engelman A, Englund G, Orenstein JM, Martin MA, Craigie R. Multiple effects of mutations in human immunodeficiency virus type I integrase on viral replication. J. Virol. 69 (5), 2729–2736 (1995).
76. Butler SL, Johnson EP, Bushman FD. Human immunodeficiency virus cDNA metabolism: notable stability of two-long terminal repeat circles. J. Virol. 76 (8), 3739–3747 (2002).
77. Pierson TC, Kieffer TL, Ruff CT, Buck C, Gange SJ, Siliciano RF. Intrinsic stability of episomal circles formed during human immunodeficiency virus type I replication. J. Virol. 76 (8), 4138–4144 (2002).
78. Nguyen TH, Khakhoulina T, Simmons A, Morel P, Trono D. A simple and highly effective method for the stable transduction of uncultured porcine hepatocytes using lentiviral vector. Cell Transplant. 14 (7), 489–496 (2005).
79. Yanez-Munoz RJ, Balaggan KS, MacNeil A et al. Effective gene therapy with nonintegrating lentiviral vectors. Nat. Med. 12 (3), 348–353 (2006).
80. Nguyen TH, Oberholzer J, Birraux J, Majno P, Morel P, Trono D. Highly efficient lentiviral vector-mediated transduction of nondividing, fully reimplantable primary hepatocytes. Mol. Ther. 6 (2), 199–209 (2002).
81. Giannini C, Morosan S, Tralhao JG et al. A highly efficient, stable, and rapid approach for ex vivo human liver gene therapy via a FLAP lentiviral vector. Hepatology 38 (1), 114–122 (2003).
82. Nguyen TH, Birraux J, Wildhaber B et al. Ex vivo lentivirus transduction and immediate transplantation of uncultured hepatocytes for treating hyperbilirubinemic Gunn rat. Transplantation 82 (6), 794–803 (2006).
83. Nguyen TH, Ferry N. Liver gene therapy: advances and hurdles. Gene Ther. 11 (Suppl. 1), S76 –S84 (2004).
84. Oertel M, Rosencrantz R, Chen YQ et al. Repopulation of rat liver by fetal hepatoblasts and adult hepatocytes transduced ex vivo with lentiviral vectors. Hepatology 37 (5), 994–1005 (2003).
85. Laconi E, Oren R, Mukhopadhyay DK et al. Long-term, near-total liver replacement by transplantation of isolated hepatocytes in rats treated with retrorsine. Am. J. Pathol. 153 (1), 319–329 (1998).
86. Cubero FJ, Maganto P, Mula N et al. Hepatic proliferation in Gunn rats transplanted with hepatocytes: effect of retrorsine and tri-iodothyronine. Cell Prolif. 38 (3), 137–146 (2005).
87. Chowdhury JR, Arias IM. Disorders of bilirubin conjugation. In: Bile Pigments and Jaundice. Ostrov JD (Ed.) Marcel Dekker, NY, USA 317–332 (1986).
88. Hartmann F, Bissell DM. Metabolism of heme and bilirubin in rat and human small intestinal mucosa. J. Clin. Invest. 70 (1), 23–29 (1982).
89. Medley MM, Hooker RL, Rabinowitz S, Holton R, Jaffe BM. Correction of congenital indirect hyperbilirubinemia by small intestinal transplantation. Am. J. Surg. 169 (1), 20–27 (1995).
90. Seppen J, Tada K, Ottenhoff R et al. Transplantation of Gunn rats with autologous fibroblasts expressing bilirubin UDP-glucuronosyltransferase: correction of genetic deficiency and tumor formation. Hum. Gene Ther. 8 (1), 27–36 (1997).
91. De Braekeleer M, Larochelle J. Genetic epidemiology of hereditary tyrosinemia in Quebec and in Saguenay-Lac-St-Jean. Am. J. Hum. Genet. 47 (2), 302–307 (1990).
92. Kvittingen EA, Brodtkorb E. The pre- and post-natal diagnosis of tyrosinemia type I and the detection of the carrier state by assay of fumarylacetoacetase. Scand. J. Clin. Lab. Invest. Suppl. 184, 35–40 (1986).
93. Tanguay RM, Jorquera R, Poudrier J, St-Louis M. Tyrosine and its catabolites: from disease to cancer. Acta Biochim. Pol. 43 (1), 209–216 (1996).
94. Paradis K. Tyrosinemia: the Quebec experience. Clin. Invest. Med. 19 (5), 311–316 (1996).
95. Lindstedt S, Holme E, Lock EA, Hjalmarson O, Strandvik B. Treatment of hereditary tyrosinaemia type I by inhibition of 4-hydroxyphenylpyruvate dioxygenase. Lancet 340 (8823), 813–817 (1992).
96. Kvittingen EA, Rootwelt H, Brandtzaeg P, Bergan A, Berger R. Hereditary tyrosinemia type I. Self-induced correction of the fumarylacetoacetase defect. J. Clin. Invest. 91 (4), 1816–1821 (1993).
97. Grompe M, Lindstedt S, al-Dhalimy M et al. Pharmacological correction of neonatal lethal hepatic dysfunction in a murine model of hereditary tyrosinaemia type I. Nat. Genet. 10 (4), 453–460 (1995).
98. Luijerink MC, Jacobs SM, van Beurden EA et al. Extensive changes in liver gene expression induced by hereditary tyrosinemia type I are not normalized by treatment with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC). J. Hepatol. 39 (6), 901–909 (2003).
99. Hacein-Bey-Abina S, Le Deist F, Carlier F et al. Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy. N. Engl. J. Med. 346 (16), 1185–1193 (2002).
100. Overturf K, al-Dhalimy M, Ou CN et al. Adenovirus-mediated gene therapy in a mouse model of hereditary tyrosinemia type I. Hum. Gene Ther. 8 (5), 513–521 (1997).
101. Chen SJ, Tazelaar J, Moscioni AD, Wilson JM. In vivo selection of hepatocytes transduced with adeno-associated viral vectors. Mol. Ther. 1 (5 Pt 1), 414–422 (2000).
102. Balciunas D, Wangensteen KJ, Wilber A et al. Harnessing a high cargo-capacity transposon for genetic applications in vertebrates. PLoS Genet. 2 (11), e169 (2006).
103. Montini E, Held PK, Noll M et al. In vivo correction of murine tyrosinemia type I by DNA-mediated transposition. Mol. Ther. 6 (6), 759–769 (2002).
104. Held PK, Olivares EC, Aguilar CP, Finegold M, Calos MP, Grompe M. In vivo correction of murine hereditary tyrosinemia type I by phiC31 integrase-mediated gene delivery. Mol. Ther. 11 (3), 399–408 (2005).
105. Overturf K, Al-Dhalimy M, Manning K, Ou CN, Finegold M, Grompe M. Ex vivo hepatic gene therapy of a mouse model of hereditary tyrosinemia type I. Hum. Gene Ther. 9 (3), 295–304 (1998).
106. Lagasse E, Connors H, Al-Dhalimy M et al. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat. Med. 6 (11), 1229–1234 (2000).
107. Wang X, Montini E, Al-Dhalimy M, Lagasse E, Finegold M, Grompe M. Kinetics of liver repopulation after bone marrow transplantation. Am. J. Pathol. 161 (2), 565–574 (2002).
108. Thorgeirsson SS, Grisham JW. Hematopoietic cells as hepatocyte stem cells: a critical review of the evidence. Hepatology 43 (1), 2–8 (2006).
109. Vassilopoulos G, Wang PR, Russell DW. Transplanted bone marrow regenerates liver by cell fusion. Nature 422 (6934), 901–904 (2003).
110. Wang X, Willenbring H, Akkari Y et al. Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature 422 (6934), 897–901 (2003).
111. Willenbring H, Bailey AS, Foster M et al. Myelomonocytic cells are sufficient for therapeutic cell fusion in liver. Nat. Med. 10 (7), 744–748 (2004).
112. Holme E, Lindstedt S. Tyrosinaemia type I and NTBC (2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione). J. Inherit. Metab. Dis. 21 (5), 507–517 (1998).
113. Holme E, Lindstedt S. Nontransplant treatment of tyrosinemia. Clin. Liver Dis. 4 (4), 805–814 (2000).
114. Mitchell C, Mignon A, Guidotti JE et al. Therapeutic liver repopulation in a mouse model of hypercholesterolemia. Hum. Mol. Genet. 9 (11), 1597–1602 (2000).
115. Hacein-Bey-Abina S, Von Kalle C, Schmidt M et al. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 302 (5644), 415–419 (2003).
116. Wu X, Li Y, Crise B, Burgess SM. Transcription start regions in the human genome are favored targets for MLV integration. Science 300 (5626), 1749–1751 (2003).
117. Montini E, Cesana D, Schmidt M et al. Hematopoietic stem cell gene transfer in a tumor-prone mouse model uncovers low genotoxicity of lentiviral vector integration. Nat. Biotechnol. 24 (6), 687–696 (2006).
118. Nguyen TH, Bellodi-Privato M, Aubert D et al. Therapeutic lentivirus-mediated neonatal in vivo gene therapy in hyperbilirubinemic Gunn rats. Mol. Ther. 12 (5), 852–859 (2005).
119. Beaty RM, Jackson M, Peterson D et al. Delivery of glucose-6-phosphatase in a canine model for glycogen storage disease, type Ia, with adeno-associated virus (AAV) vectors. Gene Ther. 9 (15), 1015–1022 (2002).
120. Zingone A, Hiraiwa H, Pan CJ et al. Correction of glycogen storage disease type Ia in a mouse model by gene therapy. J. Biol. Chem 275 (2), 828–832 (2000).
121. Kiang A, Hartman ZC, Liao S et al. Fully deleted adenovirus persistently expressing GAA accomplishes long-term skeletal muscle glycogen correction in tolerant and nontolerant GSD-II mice. Mol. Ther. 13 (1), 127–134 (2006).
122. Sun B, Zhang H, Franco LM et al. Efficacy of an adeno-associated virus 8-pseudotyped vector in glycogen storage disease type II. Mol. Ther. 11 (1), 57–65 (2005).
123. Mount JD, Herzog RW, Tillson DM et al. Sustained phenotypic correction of hemophilia B dogs with a Factor IX null mutation by liver-directed gene therapy. Blood 99 (8), 2670–2676 (2002).
124. Chung S, Ma X, Liu Y, Lee D, Tittiger M, Ponder KP. Effect of neonatal administration of a retroviral vector expressing α-L-iduronidase upon lysosomal storage in brain and other organs in mucopolysaccharidosis I mice. Mol. Genet. Metab. 90 (2), 181–192 (2007).
125. Ponder KP, Melniczek JR, Xu L et al. Therapeutic neonatal hepatic gene therapy in mucopolysaccharidosis VII dogs. Proc. Natl Acad. Sci. USA 99 (20), 13102–13107 (2002).
126. Harding CO, Gillingham MB, Hamman K et al. Complete correction of hyperphenylalaninemia following liver-directed, recombinant AAV2/8 vector-mediated gene therapy in murine phenylketonuria. Gene Ther. 13 (5), 457–462 (2006).
127. Ding Z, Georgiev P, Thony B. Administration-route and gender-independent long-term therapeutic correction of phenylketonuria (PKU) in a mouse model by recombinant adeno-associated virus 8 pseudotyped vector-mediated gene transfer. Gene Ther. 13 (7), 587–593 (2006).
128. Papapetrou EP, Zoumbos NC, Athanassiadou A. Genetic modification of hematopoietic stem cells with nonviral systems: past progress and future prospects. Gene Ther. 12 (Suppl. 1), S118 –S130 (2005).